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VIROLOGY

Publisher:
Elsevier
ISSN:
0042-6822
Category:
VIROLOGY
Impact factor:
2.8
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96 parsed articles

Last update: 2026-10-28

Latest articles

RSV, influenza, and COVID-19 in hospitalized children: A comparative analysis of the 2025/2026 epidemic season in Poland

2027-01-31

Piotr Rzymski, Ilona Małecka, Barbara Szczepańska, Zuzanna Wasielewska, Małgorzata Pawłowska, Kamila Cywińska, Anna Dobrzeniecka, Jan Świerczyński, Barbara Poniedziałek, Robert Flisiak, Dorota Zarębska-Michaluk

Comparative data on the epidemiology and clinical impact of RSV, influenza, and SARS-CoV-2 infections among hospitalized children during the same epidemic season remain limited in Central Europe. This multicenter retrospective study compared the epidemiological characteristics, clinical presentations, and outcomes of laboratory-confirmed respiratory syncytial virus (RSV), influenza, and COVID-19 among hospitalized children in Poland during. A total of 756 patients were evaluated, including 408 with influenza (54.0%), 204 with COVID-19 (27.0%), and 144 with RSV (19.0%). The infections displayed distinct temporal patterns, peaking sequentially from early autumn (COVID-19) through winter (influenza) and early spring (RSV). Demographically, hospitalizations for RSV infection and COVID-19 skewed toward infants and young children (mean ages 1.8 and 2.3 years, respectively), whereas influenza affected a broader age spectrum, extending into (pre)school-aged cohorts (mean age 4.5 years; p < 0.0001). RSV infection was associated with the highest requirement for oxygen support (41.7%) and the longest hospital stay (mean, 6.0 days) compared with influenza and COVID-19 (p < 0.0001). Conversely, pneumonia was most frequently diagnosed in the COVID-19 group (16.2%; p = 0.01), which also exhibited unique elevations in D-dimer levels (p = 0.02). Vaccine and immunoprophylaxis uptake hovered near zero across all cohorts (∼1%). Empirical antibiotic use was highly prevalent (26.6%), exceeding objective pneumonia rates by two-to three-fold. Major pediatric respiratory viruses maintain unique clinical and demographic footprints. The observed low immunization rates and disproportionate antibiotic use underscore an urgent need for targeted pediatric vaccination campaigns and antimicrobial stewardship programs.

DOI: 10.1016/j.virol.2026.111104

Antiviral activity of lapachol and synthetic hydroxynaphthoquinone derivatives against Mayaro virus

2027-01-31

Pâmela Jóyce Previdelli da Conceição, Gabriela Miranda Ayusso, Tamara de Carvalho, Maria Letícia Duarte Lima, Bruna Fleck Godoi, Jéssica Damasceno Bueno, Mikaela dos Santos Marinho, Giuliana Lingua, Tomás Isaac Gomez, Juan Javier Aguilar, Paola Elaine Galán-Jurado, José González-Santamaría, Cintia Bittar, Brenda S. Konigheim, Bo Zhang, Ana Carolina Gomes Jardim, Flávio da Silva Emery, Paula Rahal, Marília Freitas Calmon

The Mayaro virus (MAYV) is an arbovirus belonging to the Togaviridae family, genus Alphavirus. MAYV causes several sporadic outbreaks, affecting regions of the Americas. There are no specific antivirals for treating the disease. Therefore, studies are increasingly needed to discover effective antivirals against these neglected viruses. Thus, our study investigates the antiviral potential in vitro of a natural hydroxynaphthoquinone (QHM0001 - lapachol) and its synthetic derivatives (QHM0011, 0020 and 0110) against CMV-MAYV-nanoluc. We observed that the compounds QHM0001, 0011, 0020 and 0110 interfered with the post-entry stages (2 h.p.i.) of the CMV-MAYV-nanoluc, suggesting an effect on the viral genome replication stage. QHM0001, 0011 and 0020 showed high percentages of inhibition in late stages (4, 6 and 8 h.p.i.) of CMV-MAYV-nanoluc replication cycle. Thus, our study highlights the potential of the tested hydroxynaphthoquinones as promising candidates for new broad-spectrum antivirals.

DOI: 10.1016/j.virol.2026.111107

Single-cell transcriptomic landscape of avian influenza H9N2 virus infection in human and chicken cells

2027-01-31

Fanny Oldensand, Nima Rafati, Vincent Van Hoef, Åke Lundkvist, Mahmoud Darweesh, Patrik Ellström, Mahmoud M. Naguib

Avian influenza viruses circulate naturally among migratory wild birds but can occasionally infect other species, including poultry and a broad range of mammals and humans. Although highly pathogenic avian influenza viruses (AIVs) are known to infect humans, low-pathogenic AIVs, particularly H7N9 and H9N2 subtypes, have also caused human infections and pose an ongoing zoonotic risk. In this study, we used single-cell transcriptomics to examine the cellular responses of human (A549) and chicken (DF-1) cells 24 h after infection with the zoonotic H9N2 virus. Our findings revealed distinct transcriptional responses between the two cell lines. Notably, dipeptidyl peptidase-4 (DPP4) and carboxypeptidase Q (CPQ) genes were expressed at significantly higher levels in infected DF-1 cells than in A549 cells, suggesting a potential role in viral replication. Overexpression of CPQ and DPP4 in A549 cells resulted in significantly greater viral replication compared to mock-transfected wild-type cells infected with the avian influenza H9N2 virus. Furthermore, Gene Set Enrichment Analysis of differentially expressed genes revealed downregulation of lipid metabolism pathways in cell clusters highly expressing H9N2 virus genes in both A549 and DF-1 cells, indicating a potential link between host lipid metabolism and H9N2 virus replication. These results provide insights into the transcriptional responses of A549 and DF-1 cells to H9N2 infection and identify candidate host factors and pathways associated with viral replication. These findings provide a foundation for future studies using physiologically relevant models to investigate the cellular determinants of H9N2 infection.

DOI: 10.1016/j.virol.2026.111070

No receptor-binding domain adaptation detected in within-host H5N1 surveillance of 4,559 US dairy outbreak sequences

2027-01-31

Hayden Farquhar

Background The 2024–2026 US H5N1 clade 2.3.4.4b dairy cattle outbreak has been characterised primarily through consensus-level phylogenetics. Whether mammalian-adaptation variants are emerging at sub-consensus frequencies within infected hosts, particularly at the haemagglutinin receptor-binding domain (RBD), remains unknown because no systematic within-host variant analysis of the public sequencing corpus has been performed. Methods We conducted a pre-registered, corpus-wide intrahost single-nucleotide variant (iSNV) analysis of all publicly available H5N1 cattle, feline-spillover, and retail-milk sequences on the NCBI Sequence Read Archive (4,559 samples across 7 BioProjects). A dual-caller concordance pipeline (iVar + LoFreq) with empirically determined allele frequency (AF) threshold (3%, set via four-criterion validation including synthetic spike-in controls) was applied to an 11-site Tier 1 mammalian-adaptation panel spanning the polymerase complex, haemagglutinin RBD, and accessory proteins. Within-host nucleotide diversity was compared across host categories. Results The HA RBD sites Q226L and G228S (H3 numbering) showed zero detections across >4,300 adequately sequenced samples at all AF thresholds tested (1–5%), despite the pipeline detecting other non-synonymous variants at these exact codon positions (upper 95% CI for prevalence: 0.08%). Seven of eleven adaptation sites carried statistically significant iSNV signals after Bonferroni correction (corrected α = 0.00417), though all at low prevalence (≤2.95%). Genotype stratification showed that most polymerase-site detections reflected genotype structure rather than within-host emergence: the apparent PB2 631 L→M “reversion” was largely the ancestral avian state of the D1.1 genotype (20 of 23 detections), which never acquired the 631L mammalian adaptation, with only two genuine sub-consensus events in the B3.13 background, while consensus-level PB2 701N was a fixed feature of the D1.1 genotype (10 of 14 detections) rather than independent sub-consensus emergence. Cattle exhibited significantly higher within-host nucleotide diversity than feline-spillover samples (π = 1.59 × 10 -4 vs 6.11 × 10 -5 ; Kruskal–Wallis p = 6.6 × 10 -15 ), a finding that persisted after depth-matching (p = 4.6 × 10 -5 ); this may reflect prolonged mammary-gland infection, though sampling differences and host biology cannot be excluded. Conclusions We did not detect HA receptor-switching adaptation (the acquisition of human-type α2,6 receptor binding via Q226L/G228S) at any tested allele frequency in the US dairy H5N1 outbreak. Sub-consensus mammalian-adaptation signals exist at polymerase-complex sites but at low prevalence, are genotype-structured rather than independently recurrent, and require functional characterisation before informing risk assessment.

DOI: 10.1016/j.virol.2026.111073

Evaluating sampling strategies for the detection of avian influenza viruses in the environment

2027-01-31

Allison K. Miller, Lia Heremia, Stephanie J. Waller, Sarah-Lou Blanchard, Jordan T. Taylor, Jackson M. Treece, Michelle Wille, Neil J. Gemmell, David Winter, Edwina J. Dowle, Jemma L. Geoghegan

Highly pathogenic avian influenza (HPAI) viruses pose an increasing threat to wildlife, livestock and human health, underscoring the need for scalable and early-warning surveillance systems. Environmental RNA (eRNA) monitoring offers a non-invasive, cost-effective alternative to traditional host-based sampling by detecting viral genetic material shed into the environment. Despite its utility, the relative performance of different environmental sampling approaches for avian influenza virus (AIV) detection remains poorly resolved. Here, we conducted a longitudinal study with monthly sampling over approximately one year across two urban waterfowl ponds in Aotearoa New Zealand to evaluate four eRNA sampling strategies - fresh faeces, sediment, active-filtered water and passive-filtered water - for their ability to detect AIV. Using a combination of metagenomic sequencing and RT-qPCR, we show that all sample types can detect AIV, although detections were highly inconsistent across sampling methods, locations and time points. While metagenomic sequencing provided valuable genomic data, including subtype identification and phylogenetic context, RT-qPCR exhibited greater sensitivity, with active-filtered water yielding the highest detection rates, and is currently the more cost-effective approach for large-scale surveillance. Notably, AIV detections were asynchronous among sample types and frequently lacked temporal concordance, suggesting that environmental heterogeneity, RNA persistence, and methodological detection limits strongly influence surveillance outcomes. Despite these inconsistencies, phylogenetic analyses revealed that detected viruses belong to established Australasian lineages, highlighting the ability of environmental surveillance to capture ecologically relevant viral diversity. Our findings demonstrate that while eRNA-based surveillance holds substantial promise as a complementary tool for AIV monitoring, its effectiveness is highly dependent on the environmental sampling strategies and laboratory detection methods used.

DOI: 10.1016/j.virol.2026.111069

Dengue virus disease phenotypes in C57BL/6N Ifnar1 −/− Ifngr1 −/− mice

2027-01-31

Kitiya Piboonprai, Ayae Nishiyama, Takuto Nogimori, Tomokazu Tamura, Takasuke Fukuhara, Shokichi Takahama, Takuya Yamamoto

Dengue virus (DENV) remains a major global health problem, and experimentally tractable animal models are essential for investigating severe dengue pathogenesis and antiviral or vaccine strategies. However, whereas interferon receptor-deficient mouse models are used, the disease phenotype in C57BL/6N Ifnar1-/- Ifngr1-/- double-knockout (DKO) mice has not been sufficiently characterized. Here, we generated and characterized C57BL/6N-based DKO mice deficient in both type I and type II interferon receptors (Ifnar1-/- Ifngr1-/-). We first assessed susceptibility to DENV-2 NGC infection in wild-type, single-knockout, and DKO mice and found that combined Ifnar1 and Ifngr1 loss was required for rapid and severe disease. DENV-2 NGC-infected DKO mice exhibited marked weight loss, severe clinical manifestations, and 100% mortality. We then performed phenotypic screening using selected DENV serotype 1-4 strains under strain-specific inoculation conditions. This revealed strain- and condition-dependent differences in disease outcomes, and DENV-2 NGC was selected for further characterization based on the rapid lethal disease observed under the conditions used. Detailed characterization of DENV-2 NGC infection demonstrated progressive viral RNA accumulation in multiple organs, including the liver, brain, spleen, and large intestine, and infectious virus was detected in selected peripheral tissues. Histopathological analyses revealed multi-organ tissue alterations with inflammatory changes and vascular abnormalities, and Evans blue extravasation assays demonstrated increased vascular permeability in infected tissues. Collectively, these findings establish a C57BL/6N-based Ifnar1-/- Ifngr1-/- mouse platform for studying DENV-2 NGC-induced severe disease phenotypes and provide a practical framework for future mechanistic and preclinical studies on antiviral or vaccine strategies.

DOI: 10.1016/j.virol.2026.111106

A novel human G11P[25] rotavirus strain in Japan with a mosaic genome representing porcine, human, and feline rotavirus lineages

2027-01-31

Satoshi Komoto, Yumi Ushikai, Kiyoko Amo, Yuki Akari, Saori Fukuda, Tatsuya Shirai, Hideo Okuno, Naomi Sakon

Human G11P[25] rotaviruses reported to date have been porcine-like strains with relatively conserved Wa-like genomic backbones. A novel human G11P[25] strain, RVA/Human-wt/JPN/S22-592/2023/G11P[25] (short name, S22-592), was detected in stool from a 17-year-old boy hospitalized with severe gastroenteritis in Japan. In this study, we sequenced and characterized the whole genome of strain S22-592. Whole-genome analysis revealed a unique genotype constellation, G11-P[25]-I12-R2-C3-M3-A3-N2-T3-E1-H1. Phylogenetic analysis and sequence comparisons indicated that five of the 11 genomic segments (VP7, VP4, VP6, NSP4, and NSP5) are most similar to those of Korean porcine-like human G11P[25] CAU12-2-like strains, which possess the genotype constellation G11-P[25]-I12-R1-C1-M1-A1-N1-T1-E1-H1, representing an I12-containing Wa-like backbone. Of the remaining segments, VP1 and NSP1-NSP3 are most closely related to Chinese feline-like human G3P[9] 2020999/23582009-like strains, which have the genotype constellation G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3, whereas VP2 and VP3 are most closely related to Thai/Japanese human G3P[9] B2682/To16-11-like strains, which have the genotype constellation G3-P[9]-I3-R3-C3-M3-A3-N3-T3-E3-H6. Together, these findings expand the known range of human G11P[25] rotaviruses beyond the relatively conserved porcine-like/Wa-like lineages described previously, and suggest that S22-592 represents a genomic mosaic assembled from segment groups with distinct porcine-, human-, and feline-associated evolutionary histories.

DOI: 10.1016/j.virol.2026.111111

HA1-T138A and HA1-Q226L substitutions in H3N2 canine influenza virus contribute to binding to human-type α2,6-linked sialic acid receptors

2027-01-31

Wataru Sekine, Haruhiko Kamiki, Hiroho Ishida, Hiromichi Matsugo, Kosuke Ohira, Misa Katayama, Ayano Ichikawa, Yuta Wakabayashi, Akiko Takenaka-Uema, Shin Murakami, Taisuke Horimoto

The H3N2 canine influenza A virus (IAV), which originated from an H3N2 avian IAV, has caused outbreaks in North America and Asia. Although H3N2 canine IAV has not been reported to transmit to humans, understanding the molecular basis of receptor tropism changes is important for viral surveillance and zoonotic risk assessment. For avian-like IAVs to spill over into humans, the hemagglutinin (HA) glycoprotein on the viral surface must acquire mutations that enable binding to α2,6-linked sialic acids (SA), the primary receptors for human influenza viruses. Although H3N2 canine IAV preferentially binds to α2,3-linked SA, the primary receptors for avian viruses, repeated mutations during viral replication in dogs may lead to HA substitutions that confer binding affinity to α2,6-linked SA. In this study, we serially passaged conditionally replicating H3N2 canine IAV in α2,3-linked SA-knockout MDCK cells, which predominantly express α2,6-linked SA (human-type cells), to identify mutations in the receptor-binding domain. We then generated recombinant viruses carrying individual mutations using reverse genetics and evaluated their growth properties in human-type cells. The HA1-T138A and HA1-Q226L substitutions significantly enhanced viral replication in these cells. Furthermore, a solid-phase glycan-binding assay demonstrated that these mutations increased binding to α2,6-linked SA to levels comparable to those observed for α2,3-linked SA. Together, these findings indicate that H3N2 canine IAV has the potential to acquire mutations that enable efficient binding to α2,6-linked SA. This study suggests that the HA1-T138A and HA1-Q226L substitutions may play critical roles in the adaptation of H3N2 canine IAV to cells expressing human-type receptors.

DOI: 10.1016/j.virol.2026.111071

Phages targeting highly prevalent Greek multidrug-resistant Pseudomonas aeruginosa clinical isolates: In vitro and in vivo data

2027-01-31

Paschalis Paranos, Nikita Zrelovs, Dimitrios Skliros, Panagiota-Christina Georgiou, Karina Svanberga, Andris Kazaks, Marios Kostakis, Nikolaos Thomaidis, Emmanouil Flemetakis, Joseph Meletiadis

Metallo-β-lactamase–producing Pseudomonas aeruginosa (MBL-PA) poses a major therapeutic challenge. In search of alternative therapeutic approaches, bacteriophages against MBL-PA were isolated from environmental and clinical samples and thoroughly characterized. Samples from a sewage treatment plant (n = 50), rectal swabs (n = 50), and stool samples (n = 10) from patients were screened. Genomic features, microbiological properties, and growth-inhibition kinetics were determined for all isolated phages. The in vivo pharmacokinetics and therapeutic efficacy of intranasally administered phages, given alone or in combination with intraperitoneally administered amikacin, were evaluated in a murine lung infection model using a clinical MBL-PA isolate. The phages exhibited variable lytic activity against 23–70% of the isolates. The median adsorption rate was 93% (range, 87–95%), the median adsorption time was 4 minutes (range, 2–12 minutes), the median latent period was 30 minutes (range, 20–40 minutes), and the median burst size was 73 PFU/infected cell (range, 48–235). All isolated phages strongly inhibited the growth of their host strains with a median (range) of 88% (56–128%) growth inhibition. In vivo, phage titers reached up to 10 7 PFU/lung in lung tissue and in bronchoalveolar lavage fluid, whereas no phages were detected in blood. Combination therapy with amikacin significantly reduced the bacterial burden by ≥2.8 log 10 CFU/lung compared with monotherapies. Strong lytic activity and a relatively broad spectrum within the tested isolate collection were observed among the isolated phages against MBL-producing P. aeruginosa isolates. Selected phages exhibited high lytic activity even at the lowest multiplicity of infection tested, making them promising candidates for further investigation in efforts to control multidrug-resistant P. aeruginosa infections, particularly when combined with antibiotics.

DOI: 10.1016/j.virol.2026.111078